influence of reproductive cycle and menopause on hiv-1 infection and tfv gel activity

Conditions: HIV Prevention

Summary: purpose of the study is to assess tenofovir (tfv) pk and pd endpoints, cervicovaginal safety parameters, susceptibility to hiv-1 infection, and objective measures of vaginal applicator use in premenopausal and postmenopausal women.

premenopausal women: baseline blood and genital samples will be taken in the follicular and luteal phase (visits 2 and 3). the participant will be given tfv gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visits 4/4a and 5/5a). postmenopausal women: premenopausal women: baseline blood and genital samples will be taken (visit 2). the participant will be given tfv gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visit 3/3a). estradiol cream will be distributed at visit 4. post estradiol blood and genital samples will be taken at visit 5. the participant will given tfv gel and instructed to insert 2 doses as before, while continuing to use the estradiol cream. post tfv gel and estradiol cream blood and genital samples will be taken (visit 6/6a).

Eligibility criteria:
inclusion criteria: all volunteers * in good healthsignificant systemic disease * not at risk of an sti, meaning: in a monogamous heterosexual or same sex relationship for at least the last four months with a partner who is not known to be hiv positive and has no known risks for stis or sexually abstinent * willing and able to comply with study procedures * normal pap smear (by written report) in the past year. inclusion criteria: premenopausal volunteers * 21-to-45 years of age * not at risk for pregnancy, meaning: * regular menstrual cycles (every 24 - 35 days) * luteal phase p level of greater than or equal to 3 ng/ml inclusion criteria: postmenopausal volunteers * 46-89 years of age or both ovaries removed at least 30 days prior to visit 1 * no menstrual periods/vaginal bleeding in the past 12 months or both ovaries removed at least 30 days prior to visit 1 * fsh level of greater than or equal to 20 miu/ml exclusion criteria: all volunteers * clinically significant history of an abnormal pap smear in the past year * surgery or biopsy of the vagina or cervix within 30 days * current sti or lower genital tract infection * current use of chronic immunosuppressants * current presence of vulvar, anal and/or vaginal genital warts * current tobacco use of any amount * history of sensitivity/allergy to any component of the study product, topical anesthetic, or allergy to silver nitrate and/or monsel's solution * known bleeding disorder that could lead to prolonged or continuous bleeding * grade 1 or higher laboratory abnormality, per the august 2009 update of the daids table for grading the severity of adverse events * systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, antivirals or antiretrovirals. * investigator discretion * current participation in any other drug or device study exclusion criteria: premenopausal women * use of dmpa in last six months * use of any other hormonal contraceptive method without 2 subsequent, normal menses since stopping hormonal contraceptives * current use of copper iud * currently pregnant or pregnancy within the past 3 months * currently breastfeeding/having breastfed an infant in the last 2 months exclusion criteria: postmenopausal women * use of any hormonal medications in the past 30 days * contraindications to vaginal estrogen cream